7-deazaadenine and 5-chlorouracil

A modified DNA aptamer that binds BACE1, a therapeutic target involved in Alzheimer's disease has been developed. This ssXNA not only tightly binds to BACE1 but also inhibits its protease activity in vitro in the same range as a previously described unmodified aptamer. We report the in vitro selection of functional oligonucleotides incorporating two nucleobase modifications: 5-chlorouracil and 7-deazaadenine. The nucleoside analogue 5-chloro-2'-deoxyuridine has already been explored as a replacement for thymidine in a chemically modified genome of a bacterium. Thus, 5-chlorouracil modification is a good candidate to support genetic transfer in vivo as well as functional activity.

Topics: Adenine; Amyloid Precursor Protein Secretases; Aptamers, Nucleotide; Aspartic Acid Endopeptidases; Base Sequence; Humans; Protein Binding; SELEX Aptamer Technique; Uracil

5-Chloro-2'-deoxyuridine as a possible component of a chemically modified genome has been discussed in terms of its influence on duplex stability and DNA polymerase incorporation properties. The search for its counterpart among different deoxyadenosine analogs (7-deaza-, 8-aza- and 8-aza-7-deaza-2'-deoxyadenosines) showed that the stable duplex formation as well as the synthesis of long constructs, more than 2 kb, were successful with the 5-chloro-2'-deoxyuridine and 7-deaza-2'-deoxyadenosine combination and with Taq DNA polymerase.

Topics: Adenine; Base Pairing; Deoxyadenosines; Deoxyuridine; DNA; Tubercidin; Uracil